**1. Introduction**

Survival in systemic lupus erythematosus (SLE) has dramatically improved over recent decades due to advancements in early diagnosis and therapies to prevent endstage organ damage, particularly at the onset of disease [1, 2]. In 1976, Urowitz et al. reported a bimodal distribution of death in SLE, with atherosclerosis identified as a leading cause of late-stage mortality [3]. Although the prevalence and severity of the atherosclerotic cardiovascular events (CVEs) have been steadily decreasing over the last decades, the standardized mortality ratio (SMR) from atherosclerosis remains threefold higher compared with the general population [4].

Atherosclerosis is an inflammatory condition characterized by the storage of lipids and the accumulation of immune cells in the media layer of the arterial wall in medium- and large-sized arteries. Progressing disease will eventually lead to ischemia and hypoperfusion or complete obstruction of the blood flow in the affected organs, which manifests as CVEs, cerebrovascular accidents (CVA or stroke), and peripheral arterial disease (PAD) [5–8]. SLE patients have an earlier onset of atherosclerosis compared with the general population, which is not completely explained by traditional risk factors [9]. SLE-related disease factors are felt to contribute substantially to premature and accelerated atherosclerotic disease [10, 11]. The pathophysiology of accelerated atherosclerosis is not completely understood, but is a consequence of complex interactions between autoimmunity, chronic inflammation, vascular repair, traditional risk factors, and medications [12, 13].

Focused efforts by clinicians must incorporate preventative strategies to reduce the impact of traditional and nontraditional cardiovascular risk factors in SLE patients. This chapter provides an overview of considerations for the mechanisms, impact, and prevention of atherosclerosis in SLE.
